title: Identification of a novel risk variant in the FUS gene in essential tremor.
abstract: OBJECTIVE
  A nonsense mutation in the amyotrophic lateral sclerosis gene FUS has been found to segregate in a large family with essential tremor (ET). Coding variants in this gene have not been comprehensively evaluated in ET. We conducted a genetic analysis of FUS for pathogenic and novel coding variants in 2 case-control cohorts among ethnic Chinese.
  
  
  METHODS
  In a study that involved 7,548 subjects, we first sequenced all the exon and exon-intronic boundaries of FUS in 84 ET samples. Potential causative variants that were identified were then genotyped in 2 separate case-control cohorts involving 263 additional ET samples and 5,919 controls (set 1) and 250 ET cases and 250 controls (set 2), and 782 diseased controls of Chinese ethnicity from 2 different Asian countries.
  
  
  RESULTS
  We identified a novel variant, Met392Ile, in exon 12 of the FUS gene. This variant was associated with ET in set 1 (odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). The association was subsequently validated in set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4)). No association was observed in another neurologic cohort of patients with Parkinson disease, and no other potential pathogenic mutations were identified.
  
  
  CONCLUSIONS
  We identified a novel risk variant, Met392Ile, in the FUS gene that increases susceptibility of ET among ethnic Chinese. Further studies in other ethnic populations are needed to determine whether this is an ethnic-specific risk factor.
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
authors.forename: Jia Nee
authors.initials: JN
authors.lastname: Foo
authors.forename: Louis C S
authors.initials: LC
authors.lastname: Tan
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
authors.forename: Kumar M
authors.initials: KM
authors.lastname: Prakash
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.forename: Wing-Lok
authors.initials: WL
authors.lastname: Au
authors.forename: Chia Wen
authors.initials: CW
authors.lastname: Chang
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D020329:Essential Tremor / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D012307:Risk Factors
chemical_list: D018389:Codon, Nonsense; D034702:RNA-Binding Protein FUS